AR040350A1 - Inhibidores de caspasa y usos de los mismos - Google Patents

Inhibidores de caspasa y usos de los mismos

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Publication number
AR040350A1
AR040350A1 ARP030102352A ARP030102352A AR040350A1 AR 040350 A1 AR040350 A1 AR 040350A1 AR P030102352 A ARP030102352 A AR P030102352A AR P030102352 A ARP030102352 A AR P030102352A AR 040350 A1 AR040350 A1 AR 040350A1
Authority
AR
Argentina
Prior art keywords
disease
halo
straight
ocf3
branched
Prior art date
Application number
ARP030102352A
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English (en)
Inventor
Michael Mortimore
Ronald Knegtel
John Studley
David Millan
Original Assignee
Vertex Pharma
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Publication date
Application filed by Vertex Pharma filed Critical Vertex Pharma
Publication of AR040350A1 publication Critical patent/AR040350A1/es

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    • C07D239/72—Quinazolines; Hydrogenated quinazolines
    • C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
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    • C07D217/24—Oxygen atoms

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  • Health & Medical Sciences (AREA)
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Abstract

Reivindicación 1: Un compuesto de fórmula (1), en donde: X es un CH o N; Y es halo, trifluorfenoxi o tetrafluorfenoxi; R2 es alquilo C1-6 de cadena recta o ramificada; R3 es hidrógeno, halo, OCF3, CN o CF3; y R4 es hidrógeno, halo, OCF3, SR, CN, CF3, Ar o T-Ar; en donde: T es O ó S; R es un alquilo C1-6 de cadena recta o ramificada; Ar es un anillo fenilo opcionalmente sustituido con 1 a 3 grupos seleccionados entre halo, CH3, CF3, CN, OMe, OCF3 y NR5R6; y R5 y R6 son, cada uno en forma independiente, H o alquilo C1-6 de cadena recta o ramificada, o R5 y R6, tomados juntos, forman un anillo de 5 a 7 miembros que opcionalmente contiene hasta 3 heteroátomos seleccionados entre O, S, NH y N(alquilo C1-6 de cadena recta o ramificada); siempre que Y sea halo, entonces R3 y R4 no son simultáneamente hidrógeno. Reivindicación 21: Una composición farmacéutica que comprende: a) un compuesto conforme a cualquiera de las reivindicaciones 1 a 20; b) un portador, adyuvante o vehículo farmacéuticamente aceptable. Reivindicación 22: Un método para tratar una enfermedad en un paciente, en donde dicha enfermedad se selecciona entre una enfermedad regulada por IL-1,una enfermedad regulada por apoptosis, una enfermedad inflamatoria, una enfermedad autoinmune, un trastorno óseo destructivo, un trastorno proliferativo, una enfermedad infecciosa, una enfermedad degenerativa, una enfermedad asociada con la muerte celular, una enfermedad por ingestión de exceso de alcohol dietario, una enfermedad regulada viral, trastornos de la retina, uveítis, peritonitis inflamatoria, osteoartritis, pancreatitis, asma, síndrome de insuficiencia respiratoria del adulto, glomerulonefritis, artritis reumatoidea, lupus eritematoso sistémico, esclerodermia, tiroiditis crónica, enfermedad de Grave, gastritis autoinmune, diabetes, anemia hemolítica autoinmune, neutropenia autoinmune, trombocitopenia, hepatitis activa crónica, miastenia grave, enfermedad intestinal inflamatoria, enfermedad de Crohn, psoriasis, dermatitis atópica, cicatrización patológica, enfermedad de injerto contra huésped, rechazo de transplante de órganos, apoptosis de órganos luego de danos por quemaduras, osteoporosis, leucemias y trastornos relacionados, síndrome mielodisplásico, trastorno óseo relacionado con mieloma múltiple, leucemia mielógena aguda, leucemia mielógena crónica, melanoma metastático, sarcoma de Kaposi, mieloma múltiple, choque hemorrágico, sepsis, choque séptico, quemaduras, siguelosis, mal de Alzheimer, enfermedad de Parkinson, enfermedad de Huntington, enfermedad de Kennedy, enfermedad priónica, isquemia cerebral, epilepsia, isquemia de miocardio, enfermedad cardiaca aguda y crónica, infarto de miocardio, insuficiencia cardiaca congestiva, aterosclerosis, derivación aortocoronaria (bypass), atrofia muscular espinal, esclerosis lateral amiotrófica, esclerosis múltiple, encefalitis relacionada con HIV, envejecimiento, alopecia, dano neurológico debido a apoplejía, colitis ulcerativa, dano cerebral traumático, dano de la medula espinal, hepatitis B, hepatitis C, hepatitis G, fiebre amarilla, fiebre del dengue, o encefalitis japonesa, varias formas de enfermedad hepática, enfermedad renal, enfermedad del rinón poliquística, enfermedad ulcerosa duodenal y gástrica asociada con H. Pylori, infección de HIV, tuberculosis, meningitis, insuficiencia de órganos, tratamiento de complicaciones asociadas con derivaciones aortocoronarias (bypass), y una inmunoterapia para el tratamiento de varias formas de cáncer; en donde dicho método comprende la etapa de administrar a dicho paciente una composición farmacéutica conforme a la reivindicación 21. Reivindicación 31: Un método de preparación de un compuesto de fórmula (1), en donde dicho método comprende: hacer reaccionar un ácido o derivado ácido de fórmula (2), con un amino alcohol de fórmula (4), para proporcionar un compuestos de fórmula (3); convertir el intermediario (3) en compuesto (1), en donde: X es CH o N; Y es halo, trifluorfenoxi o tetrafluorfenoxi; R2 es alquilo C1-6 de cadena recta o ramificada; R3 es hidrógeno, halo, OCF3, CN o CF3; y R4 es hidrógeno, halo, OCF3, SR, CN, CF3, Ar o T-Ar; en donde: T es O ó S; R es un alquilo C1-6 de cadena recta o ramificada; Ar es un anillo fenilo opcionalmente sustituido con 1 a 3 grupos seleccionados entre halo, CH3, CF3,CN, OMe, OCF3 y NR5R6; R5 y R6 son, cada uno en forma independiente, H o alquilo C1-6 de cadena recta o ramificada, o R5 y R6, tomados juntos, forman un anillo de 5 a 7 miembros que opcionalmente contiene hasta 3 heteroátomos seleccionados entre O, S, NH y N(alquilo C1-6 de cadena recta o ramificada); y R7 es un grupo protector adecuado; siempre que cuando Y es halo, entonces R3 y R4 no son simultáneamente hidrógeno. Reivindicación 32: Un compuesto de fórmula (5), en donde: X es CH o N; R2 es alquilo C1-6 de cadena recta o ramificada; R3 es hidrógeno, halo, OCF3, CN o CF3; y R4 es hidrógeno, halo, OCF3, SR, CN, CF3, Ar o T-Ar; en donde: T es O ó S; R es un alquilo C1-6 de cadena recta o ramificada; Ar es un anillo fenilo opcionalmente sustituido con 1 a 3 grupos seleccionados entre halo, CH3, CF3, CN, OMe, OCF3 y NR5R6; y R5 y R6 son, cada uno en forma independiente, H o alquilo C1-6 de cadena recta o ramificada, o R5 y R6, tomados juntos, forman un anillo de 5 a 7 miembros que opcionalmente contiene hasta 3 heteroátomos seleccionados entre O, S, NH y N(alquilo C1-6 de cadena recta o ramificada).
ARP030102352A 2002-06-28 2003-06-27 Inhibidores de caspasa y usos de los mismos AR040350A1 (es)

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CA2493646A1 (en) 2004-01-08
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BR0312232A (pt) 2005-05-10
US20040072850A1 (en) 2004-04-15
UY27872A1 (es) 2003-12-31
JP2005533825A (ja) 2005-11-10
IL165986A0 (en) 2006-01-15
MXPA05000069A (es) 2005-04-11
EP1539701A1 (en) 2005-06-15
AU2003248758A1 (en) 2004-01-19
CN1675184A (zh) 2005-09-28
NZ537807A (en) 2007-05-31
TW200404783A (en) 2004-04-01
NO20050851L (no) 2005-03-29
PE20040728A1 (es) 2004-10-23
JP4616643B2 (ja) 2011-01-19

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